Beyond DNA: RNA editing and steps toward Alu exonization in primates

Area of Science:

• Evolutionary biology
• Molecular genetics
• Genomics

Background:

• Exonization of transposed elements generates novel gene functions.
• Adenosine-to-inosine (A-to-I) RNA editing can mediate exonization of intronic sequences.
• Alternative splicing of introns into mRNA is a key mechanism for protein diversification.

Purpose of the Study:

• To investigate the evolutionary origin and mechanism of an RNA-editing-mediated exonization event.
• To identify the role of A-to-I editing in generating alternative splice variants in the nuclear prelamin A recognition factor gene.
• To trace the evolutionary history of this exonization event across primate species.

Main Methods:

• Comparative genomics and sequence analysis of primate nuclear prelamin A recognition factor genes.
• RNA sequencing and analysis of mRNA clones from various primate species.
• Identification and characterization of A-to-I editing sites and alternative splice variants.

Main Results:

• The alternatively spliced exon 8 in the human nuclear prelamin A recognition factor gene originated from an intronic Alu element via A-to-I editing.
• This exonization event occurred in an anthropoid ancestor approximately 58-40 million years ago, with functional realization 34-52 million years later.
• Seven RNA-editing-mediated alternative splice variants and 30 A-to-I editing sites were identified across primate species.

Conclusions:

• A-to-I RNA editing is a significant evolutionary force contributing to exonization and the generation of novel protein functions.
• The nuclear prelamin A recognition factor gene in great apes serves as a model for understanding the interplay of RNA editing and alternative splicing in creating genetic novelty.
• This study highlights the dynamic nature of gene evolution through post-transcriptional modifications.